Metabolite to parent drug concentration ratio as a function of parent drug extraction ratio: cases of nonportal route of administration.

The ratio of metabolite to parent drug concentration (Cm/Cp) of a medium or high extraction ratio (E greater than 0.1) drug administered intravenously has been shown to depend on intrinsic clearance of drug by other metabolic routes (CLr,int) as well as on organ blood flow (Q). In contrast, for a low extraction ratio drug given intravenously or for any drug given by a portal route, this ratio is equal to the ratio of formation clearance (CLf,int) and metabolite clearance (CLm,int). The sensitivity of Cm/Cp to changes in CLr,int and CLf,int has been analyzed quantitatively. It was shown to be dependent on the fraction metabolized to that particular metabolite (fm).